Study of Phenoptin to Increase Phenylalanine Tolerance in... | NCT00272792

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Sapropterin Dihydrochloride	Experimental	Phenoptin, provided in tablets containing 100 mg of sapropterin dihydrochloride each, was administered orally once daily in the morning as the number of tablets equivalent to a 20mg/kg/day dose dissolved in 4-8 oz (120-240 mL) of water or apple juice for 6 weeks. A follow-up call or visit was made 4 weeks later during this double-blind, placebo-controlled study.	Drug: Sapropterin Dihydrochloride
Placebo	Placebo Comparator	Placebo, provided as tablets similar to Phenoptin tablets, was administered orally once daily in the morning as the number of tablets equivalent to a 20mg/kg/day dose dissolved in 4 8 oz (120-240 mL) of water or apple juice. for 6 weeks. A follow-up call or visit was made 4 weeks later during this double-blind, placebo-controlled study.	Drug: Placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Sapropterin Dihydrochloride	Drug	Phenoptin, provided in tablets containing 100 mg of sapropterin dihydrochloride each, was administered orally once daily in the morning as the number of tablets equivalent to a 20mg/kg/day dose dissolved in 4-8 oz (120-240 mL) of water or apple juice for 6 weeks. A follow-up call or visit was made 4 weeks later during this double-blind, placebo-controlled study.

Measure	Description	Time Frame
Amount of Dietary Supplemented Phenylalanine (Phe)Tolerated in Children With Phenylketonuria		at Week 10

Measure	Description	Time Frame
Change in Phenylalanine Levels From Baseline to Week 3		Baseline to Week 3

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Clinical diagnosis of PKU with hyperphenylalaninemia (HPA) documented by at least one blood Phe measurement >/=360 umol/L (6 mg/dL)
Under dietary control with a Phe-restricted diet as evidenced by:· Estimated daily Phe tolerance </=1000 mg/day
At least 6 months of blood Phe control (mean level of </=480 μmol/L) prior to enrolling in the study
Aged 4 to 12 years inclusive at screening
A blood Phe level </=480 μmol/L at screening
Female subjects of childbearing potential (as determined by the principal investigator) must have a negative blood or urine pregnancy test at entry (prior to the first dose). Note: All female subjects of childbearing potential and sexually mature male subjects must be advised to use a medically accepted method of contraception throughout the study. Female subjects of childbearing potential must be willing to undergo periodic pregnancy tests during the course of the study
Willing and able to comply with all study procedures
Willing to provide written assent (if applicable) and written informed consent by a parent or legal guardian after the nature of the study has been explained and prior to any research-related procedures

Exclusion Criteria:

Any condition that, in the view of the PI, renders the subject at high risk from treatment compliance and/or completing the study
Prior history of organ transplantation
Perceived to be unreliable or unavailable for study participation or have parents or legal guardians who are perceived to be unreliable or unavailable
Use of any investigational agent within 30 days prior to screening, or requirement for any investigational agent or vaccine prior to completion of all scheduled study assessments
ALT > 2 times the upper limit of normal (i.e., Grade 1 or higher based on World Health Organization Toxicity Criteria) at screening
Concurrent disease or condition that would interfere with study participation or safety (e.g., seizure disorder, oral steroid-dependent asthma or other condition requiring oral or parenteral corticosteroid administration, or insulin-dependent diabetes)

PubMed Identifier	Type	Citation	Retractions
19261295	Derived	Trefz FK, Burton BK, Longo N, Casanova MM, Gruskin DJ, Dorenbaum A, Kakkis ED, Crombez EA, Grange DK, Harmatz P, Lipson MH, Milanowski A, Randolph LM, Vockley J, Whitley CB, Wolff JA, Bebchuk J, Christ-Schmidt H, Hennermann JB; Sapropterin Study Group. Efficacy of sapropterin dihydrochloride in increasing phenylalanine tolerance in children with phenylketonuria: a phase III, randomized, double-blind, placebo-controlled study. J Pediatr. 2009 May;154(5):700-7. doi: 10.1016/j.jpeds.2008.11.040. Epub 2009 Mar 4.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Sapropterin Dihydrochloride	Phenoptin, provided in tablets containing 100 mg of sapropterin dihydrochloride each, was administered orally once daily in the morning as the number of tablets equivalent to a 20mg/kg/day dose dissolved in 4-8 oz (120-240 mL) of water or apple juice for 6 weeks. A follow-up call or visit was made 4 weeks later during this double-blind, placebo-controlled study.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Sapropterin Dihydrochloride	Phenoptin, provided in tablets containing 100 mg of sapropterin dihydrochloride each, was administered orally once daily in the morning as the number of tablets equivalent to a 20mg/kg/day dose dissolved in 4-8 oz (120-240 mL) of water or apple juice for 6 weeks. A follow-up call or visit was made 4 weeks later during this double-blind, placebo-controlled study.
BG001	Placebo	Placebo, provided as tablets similar to Phenoptin tablets, was administered orally once daily in the morning as the number of tablets equivalent to a 20mg/kg/day dose dissolved in 4 8 oz (120-240 mL) of water or apple juice. for 6 weeks. A follow-up call or visit was made 4 weeks later during this double-blind, placebo-controlled study.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00033 BG00112 BG00245

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Amount of Dietary Supplemented Phenylalanine (Phe)Tolerated in Children With Phenylketonuria

Posted

Mean

Standard Deviation

mg/kg/day

at Week 10

ID	Title	Description
OG000	Sapropterin Dihydrochloride	Phenoptin, provided in tablets containing 100 mg of sapropterin dihydrochloride each, was administered orally once daily in the morning as the number of tablets equivalent to a 20mg/kg/day dose dissolved in 4-8 oz (120-240 mL) of water or apple juice for 6 weeks. A follow-up call or visit was made 4 weeks later during this double-blind, placebo-controlled study.
OG001	Placebo	Placebo, provided as tablets similar to Phenoptin tablets, was administered orally once daily in the morning as the number of tablets equivalent to a 20mg/kg/day dose dissolved in 4 8 oz (120-240 mL) of water or apple juice. for 6 weeks. A follow-up call or visit was made 4 weeks later during this double-blind, placebo-controlled study.

Units	Counts
Participants	OG00033 OG00112

Title

Denominators

Categories

Title	Measurements
	OG00020.9± 15.4 OG0012.9± 4.0

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000	Compared Week 10 to Baseline.	t-test, 1 sided		<0.001							95						No	Superiority or Other
OG001	Compared Week 10 to Baseline.	t-test, 1 sided

Secondary

Change in Phenylalanine Levels From Baseline to Week 3

Posted

Mean

Standard Error

umol/L

Baseline to Week 3

ID	Title	Description
OG000	Sapropterin Dihydrochloride	Phenoptin, provided in tablets containing 100 mg of sapropterin dihydrochloride each, was administered orally once daily in the morning as the number of tablets equivalent to a 20mg/kg/day dose dissolved in 4-8 oz (120-240 mL) of water or apple juice for 6 weeks. A follow-up call or visit was made 4 weeks later during this double-blind, placebo-controlled study.
OG001	Placebo	Placebo, provided as tablets similar to Phenoptin tablets, was administered orally once daily in the morning as the number of tablets equivalent to a 20mg/kg/day dose dissolved in 4 8 oz (120-240 mL) of water or apple juice. for 6 weeks. A follow-up call or visit was made 4 weeks later during this double-blind, placebo-controlled study.

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Sapropterin Dihydrochloride	Phenoptin, provided in tablets containing 100 mg of sapropterin dihydrochloride each, was administered orally once daily in the morning as the number of tablets equivalent to a 20mg/kg/day dose dissolved in 4-8 oz (120-240 mL) of water or apple juice for 6 weeks. A follow-up call or visit was made 4 weeks later during this double-blind, placebo-controlled study.			0	33	26
EG001	Placebo	Placebo, provided as tablets similar to Phenoptin tablets, was administered orally once daily in the morning as the number of tablets equivalent to a 20mg/kg/day dose dissolved in 4 8 oz (120-240 mL) of water or apple juice. for 6 weeks. A follow-up call or visit was made 4 weeks later during this double-blind, placebo-controlled study.			0	12	8

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Contusion	Injury, poisoning and procedural complications	Systematic Assessment	EG0003 events3 affected33 at risk EG0011 events1 affected12 at risk
Excoriation	Injury, poisoning and procedural complications	Systematic Assessment	EG0003 events2 affected33 at risk EG0010 events0 affected12 at risk
Thermal Burn	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 events0 affected33 at risk EG0011 events1 affected12 at risk
Streptococcal Infection	Infections and infestations	Systematic Assessment	EG0002 events2 affected33 at risk EG0012 events2 affected12 at risk
Upper Respiratory Tract Infection	Infections and infestations	Systematic Assessment	EG0002 events2 affected33 at risk EG0011 events1 affected12 at risk
Appendicitis	Infections and infestations	Systematic Assessment	EG0000 events0 affected33 at risk EG0011 events1 affected12 at risk
Conjuctivitis Infective	Infections and infestations	Systematic Assessment	EG0000 events0 affected33 at risk EG0011 events1 affected12 at risk
Rhinitis	Infections and infestations	Systematic Assessment	EG0000 events0 affected33 at risk EG0011 events1 affected12 at risk
Viral Infection	Infections and infestations	Systematic Assessment	EG0000 events0 affected33 at risk EG0012 events1 affected12 at risk
Rhinorrhea	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0007 events7 affected33 at risk EG0010 events0 affected12 at risk
Cough	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0007 events5 affected33 at risk EG0010 events0 affected12 at risk
Pharyngolaryngeal Pain	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0005 events4 affected33 at risk EG0011 events1 affected12 at risk
Nasal Congestion	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0004 events3 affected33 at risk EG0010 events0 affected12 at risk
Abdominal Pain	Gastrointestinal disorders	Systematic Assessment	EG0006 events3 affected33 at risk EG0011 events1 affected12 at risk
Diarrhoea	Gastrointestinal disorders	Systematic Assessment	EG0005 events4 affected33 at risk EG0010 events0 affected12 at risk
Vomiting	Gastrointestinal disorders	Systematic Assessment	EG0004 events4 affected33 at risk EG0010 events0 affected12 at risk
Toothache	Gastrointestinal disorders	Systematic Assessment	EG0002 events2 affected33 at risk EG0010 events0 affected12 at risk
Aphthous Stomatitis	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected33 at risk EG0011 events1 affected12 at risk
Headache	Nervous system disorders	Systematic Assessment	EG0007 events7 affected33 at risk EG0011 events1 affected12 at risk
Rash	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0001 events1 affected33 at risk EG0014 events2 affected12 at risk
Erythema	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0002 events2 affected33 at risk EG0010 events0 affected12 at risk
Prurigo	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 events0 affected33 at risk EG0011 events1 affected12 at risk
Pyrexia	General disorders	Systematic Assessment	EG0003 events3 affected33 at risk EG0012 events2 affected12 at risk
Fatigue	General disorders	Systematic Assessment	EG0001 events1 affected33 at risk EG0012 events2 affected12 at risk
Neutrophil Count Decreased	Investigations	Systematic Assessment	EG0001 events1 affected33 at risk EG0011 events1 affected12 at risk
White Blood Cell Count Decreased	Investigations	Systematic Assessment	EG0001 events1 affected33 at risk EG0011 events1 affected12 at risk
Lymphadenopathy	Blood and lymphatic system disorders	Systematic Assessment	EG0002 events2 affected33 at risk EG0010 events0 affected12 at risk
Decreased Appetite	Metabolism and nutrition disorders	Systematic Assessment	EG0003 events2 affected33 at risk EG0010 events0 affected12 at risk
Depression	Psychiatric disorders	Systematic Assessment	EG0000 events0 affected33 at risk EG0011 events1 affected12 at risk
Mood Swings	Psychiatric disorders	Systematic Assessment	EG0000 events0 affected33 at risk EG0011 events1 affected12 at risk

Facility	Status	City	State	ZIP	Country	Contacts
		Los Angeles	California		United States

ID	Term
D020739	Brain Diseases, Metabolic, Inborn
D001928	Brain Diseases, Metabolic
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D000592	Amino Acid Metabolism, Inborn Errors
D008661	Metabolism, Inborn Errors
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases